pathophys of type 2 diabetes

Question 1

define pre-diabetes

Answer 1

Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Diagnosed by one of the following: HbA1c 5.7-6.4, fasting plasma glucose (FPG) levels 100 -125 mg/dL, or 2 hr values on the oral glucose tolerance test (OGTT) of 140- 199 mg/dL

Question 2

treatment/prevention of diabetes in pre-diabetic patients

Answer 2

5–10% loss of body weight, exercise (150 minutes/week), and metformin. Plus yearly screening for diabetes and CVD risk profile

Question 3

list values for normal fasting glucose, impaired fasting glucose, and diabetic fasting glucose

Answer 3

Normal: 126mg/dl

Question 4

list values for normal glucose tolerance, impaired glucose tolerance and diabetic glucose tolerance

Answer 4

2 hr post glucose- normal: 200mg/dl

Question 5

List values for normal, pre-diabetic and diabetic A1C

Answer 5

normal: 6.5

Question 6

diagnosis of diabetes

Answer 6

elevated A1C OR fasting plasma glucose OR glucose tolerance test

Question 7

When are pregnant women screened for gestational diabetes

Answer 7

If average risk, at 24-28 weeks. If high risk (obesity, history, glycosuria, family history), as soon as feasible then again at 24-28 weeks.

Question 8

compare glucose tolerance test in gestational diabetes to type 2 diabetes

Answer 8

Gestational diabetes: oral glucose load of 100g. Type 2: 75 g glucose

Question 9

pathogenesis of type 2 diabetes

Answer 9

Decreased insulin sensitivity (insulin resistance) followed by inability of beta cells to compensate for defects in insulin action, thus failing to secrete enough insulin

Question 10

define insulin resistance

Answer 10

Inadequate biological effects of insulin to stimulate glucose uptake in the skeletal muscle glucose and to suppress endogenous glucose production by the liver

Question 11

genetics of T2D

Answer 11

Very family oriented- 38% of siblings and 1/3 of offspring, 90-100% in monozygotic twins. NOT associated with any particular HLA gene types

Question 12

environmental factors of T2D

Answer 12

sedentary lifestyle and obesity

Question 13

describe insulin secretion in T2D

Answer 13

At first, normal or elevated insulin. Then, acute Insulin release in response to IV is glucose it lost, but prolonged response is preserved/exaggerated. Acute insulin release in response to non-glucose stimuli (amino acids) is normal, suggesting specific defect in glucoregulation.

Question 14

When is insulin required in most T2D patients

Answer 14

After 10 years, insulin secretion is diminished and insulin is necessary for control

Question 15

Prevention of insulin requirement in T2D

Answer 15

Aggressive normalization of blood glucose in early diabetes has shown long term effects on diabetes complications. Prolonged hyperglycemia produces glucose toxicity where insulin secretory capacity is impaired

Question 16

describe insulin resistance in T2D

Answer 16

Hepatic insulin resistance results in loss of insulin suppression of hepatic glucose output (fasting hyperglycemia). Insulin resistance in the skeletal muscle and fat leads to defects in insulin-mediated storage of glucose and, fat and protein (postprandial hyperglycemia)

Question 17

what is metabolic syndrome

Answer 17

aka insulin resistance syndrome- associated with T2D. Manifests as central obesity, glucose intolerance, hypertension, atherosclerosis, polycystic ovary syndrome

Question 18

biochemical manifestations of metabolic syndrome

Answer 18

altered carbohydrate metabolism, dyslipidemia, procoagulant state

Question 19

what is maturity onset diabetes of youth

Answer 19

Presents early in life with negative antibody screens and strong family history. May be due to glucokinase deficiency (MODY2). Impaired insulin secretion with minimal/no defects in insulin action. Autosomal dominant

Question 20

what is diabetic ketoacidosis

Answer 20

severe insulin deficiency leading to extreme hyperglycemia (usually glucose >300mg/dl), an increased anion gap metabolic acidosis (usually pH 5 mM).

Question 21

insulin and glucagon effect on lipolysis, ketogenesis, gluconeogenesis, glycogenesis, glycogenolysis and glycemia

Answer 21

insulin: dec, dec, dec, incr, dec, dec. Glucagon: inc, incr, incr, dec, incr, incr

Question 22

pathogenesis of diabetic ketoacidosis

Answer 22

lack of insulin/ elevated catecholamines > lipolysis >FA delivered to liver > ketogenesis in liver > acidosis. ALSO hyperglycemia > glycosuria/polyuria > osmotic diuresis (loss of electrolytes and fluid) >dehydration > decreased renal blood flow > decreased GFR reduces kidney’s ability to excrete glucose and hyperosmolarity worsens >acidosis

Question 23

anion gap calculation

Answer 23

Na-Cl-bicarb

Question 24

Signs of DKA

Answer 24

altered mental state, (40% concious, 40% drowsy, 20% comatose), dehydration, postural hypotension, tachycardia

Question 25

precipitating cause of DKA

Answer 25

The most common cause of DKA overall is infection often accompanied by misguided omission of insulin

Question 26

diagnosing DKA

Answer 26

serum glucose >200mg/dl, urinary ketones, serum beta-hydroxybutyrate

Question 27

DKA treatment

Answer 27

insulin (inhibit gluconeogenesis and ketogenesis), fluid replacement (improve circulation and perfusion)

Question 28

who gets DKA

Answer 28

usually type 1 diabetes

Question 29

most common acute complication of diabetes

Answer 29

hypoglycemia

Question 30

define hypoglycemia

Answer 30

plasma glucose <60mg/dl

Question 31

hypoglycemia symptoms

Answer 31

adrenergic (excessive secretion of epi): sweating, tremor, tachycardia, anxiety. Neuroglycopenic (dysfunction of CNS): confusion, convulsions, loss of conciousness, dizziness, headaches

Question 32

who gets hypoglycemia

Answer 32

Hypoglycemia is about 2-3 time more common in patients trying to normalize blood glucose with intensive insulin regimens ie. type 1 diabets

Question 33

what controls hypoglycemia in diabetes

Answer 33

Glucagon stimulates glycogenolysis in liver/release of glucose and epi stimulates glycogenolysis. After a variable duration of diabetes, glucagon responsiveness to hypoglycemia is lost and epinephrine becomes the primary defense against hypoglycemia. Epinephrine can be blunted in recurrent hypoglycemia. Cortisol and growth hormone also raise blood glucose, but do so much more slowly.

Question 34

what is hypoglycemia unawareness

Answer 34

patient no longer has the adrenergic warning signs of diabetes and may go into an altered mental state with no warning symptoms at all. This is more common in patients who have frequent hypoglycemia

Question 35

treatment of hypoglycemia unawareness

Answer 35

avoid hypoglycemia for 3 weeks or more

Question 36

Ddx of hypoglycemia

Answer 36

drugs (insulin, sulphonylureas), ethanol, adrenal insufficiency, renal failure (most common in T1D), insulinoma